Breast cancer is a heterogeneous disease with a high degree of diversity in histology, therapeutic response, and patient treatment outcomes. Transcriptional profiling analyses have reproducibly identified at least five major “intrinsic” subtypes of breast cancer: normal breast-like, luminal A, luminal B, HER2/Neu-enriched, and basal-like breast cancer (BBC) (Perou et al., 2000; Sorlie et al., 2001). These molecular subtypes have recently been confirmed in a comprehensive characterization of human breast tumors at the genomic, epigenetic, transcriptomic, and proteomic levels (Koboldt et al., 2012). Among these subtypes, basal-like breast cancer (BBC) is strongly associated with an aggressive phenotype and poor prognosis (Foulkes et al. 2010; Perou 2011). Unlike their luminal counterparts, BBC cells lack expression of estrogen receptor (ER) and progesterone receptor (PR), and thus largely overlap with the clinically defined “triple-negative” breast cancers (TNBC), which is also characterized by the lack of ER/PR expression (Foulkes et al, 2010; Perou 2011). The lack of these molecular targets renders BBC or TNBC cells relatively unresponsive to targeted therapies that are highly effective in the treatment of luminal breast cancer. Establishing the molecular pathogenesis of this subtype and identifying potential targets for treatment remains a key challenge for BBC/TNBC.
Kinases represent a unique population of genes that are frequently involved in tumor pathogenesis. Indeed, a large number of mutations, alterations in copy number and/or in expression level have been observed in many kinases across multiple types of human cancers. In addition, kinases are also pharmacologically tractable making inhibition of kinase activity, such as via small molecules, a highly effective strategy for cancer treatment (Zhang et al., 2009). Accordingly, there remains a need for identification of kinase(s) critical for ER/PR expression negative cells in a manner that elucidates “druggable” targets for effective long-term treatment strategies for ER/PR expression negative breast cancers, for new methods of identifying patients that are likely to benefit from the treatment strategies, and for methods of treating patients with the effective long-term treatment strategies.